Patent GB-1260686-A (GB)
Title: Spiroazetidine-ethanoanthracenes
IPC: C07D205/12
Filed: 1969-05-02
Abstract: 1,260,686. Spiroazetidine-ethanoanthracenes. E. I. DU PONT DE NEMOURS & CO. 2 May, 1969 [3 May, 1968; 2 April, 1969], No. 22636/69. Heading C2C. Novel spiroazetidine-ethanoanthracenes of the general formula wherein R 1  and R 2  are each a hydrogen or chlorine atom or a trifluoromethyl group, R 3  and R 4  are each a hydrogen atom or a methyl group, and R 5  is a hydrogen atom, a C 1-3  alkyl, allyl, 2- hydroxyethyl, 2-hydroxypropyl, 3-hydroxypropyl, 2-(2-hydroxyethoxy)ethyl, furfuryl or tetrahydrofurfuryl group, a 2-acyloxyethyl, 2- acyloxypropyl or 3-acyloxypropyl group in which the acyl radical contains from 1 to 3 carbon atoms, a 2-alkoxyethyl, 2-alkoxypropyl or 3-alkoxypropyl group in which the alkoxy radical contains 1 or 2 carbon atoms, or a monosubstituted C 1-3  alkyl group in which the substituent is a phenyl, halophenyl, methoxyphenyl, ethoxyphenyl, hydroxyphenyl, benzoyl, halobenzoyl, carboxamido or cyano group, and non-toxic, pharmaceutically acceptable acid addition salts thereof are prepared (a) by reaction of an ethanoanthracene of the general formula wherein A is a halogen atom or an unsubstituted or substituted alkyl- or aryl-sulphonate group, with ammonia or an amine of the general formula R 5 NH 2 ; (b) when R 5  is a hydrogen atom, by treatment of the corresponding spiroazetidine-ethanoanthracene of the first general formula above wherein R 5  is an allyl group with potassium tertiary-butoxide and dimethylsulphoxide, followed by aqueous hydrochloric acid; (c) when R 5  is a hydrogen atom, by hydrogenolysis of the corresponding spiroazetidineethanoanthracene of the first general formula above wherein R 5  is a benzyl group; (d) when R 5  is other than a hydrogen atom, by a suitable substitution of the corresponding spiroazetidineethanoanthracene of the first general formula above wherein R 5  is a hydrogen atom; (e) when R 5  is a 2-acyloxyethyl, 2-acyloxypropyl or 3- acyloxypropyl group, by esterification of the corresponding azetidine-ethanoanthracene of the first general formula above wherein R 5  is a 2-hydroxyethyl, 2-hydroxypropyl or 3-hydroxypropyl group; (f) when R 5  is a hydrogen atom, by reduction of the corresponding azetidine-ethanoanthracene wherein R 5  is an alkyl- or aryl-sulphonyl group; and (g) when R 5  is a hydrogen atom, by hydrolysis of the corresponding compound wherein R 5  is -COCF 3  with an aqueous or ethanolic base; followed optionally by salification of the product. 1 - p - Toluenesulphonyl - 9<SP>1</SP>,10<SP>1</SP> - dihydrospiro[azetidine-3<SP>1</SP>,11<SP>1</SP>-9,10-ethanoanthracene is prepared by the action of p-toluenesulphonamide on 11,11-Dibromomethyl-9,10-dihydro- 9,10-ethanoanthracene, which is prepared by treatment of 11,11-dibenzenesulphonyloxymethyl-9,10-dihydro-9,10-ethanoanthracene with lithium bromide. 1-Formyl-9<SP>1</SP>,10<SP>1</SP>-dihydrospiro- [azetidine-3,11<SP>1</SP>-9,10-ethanoanthracene is prepared by reaction of the corresponding 1-unsubstituted derivative with butyl formate. 1-[p-(α-Methoxymethoxy)phenylpropyl]- 9<SP>1</SP>,10<SP>1</SP> - dihydrospiro- [azetidine-3,11<SP>1</SP>-9,10-ethanoanthracene is prepared by reaction of 11,11-dibenzenesulphonyloxymethyl - 9,10 - dihydro - 9,10 - ethanoanthracene with p-(α-methoxymethoxy)phenylpropylamine. 9<SP>1</SP>,10<SP>1</SP>-Dihydrospiro[azetidine 3,11<SP>1</SP>-9,10- ethanoanthracene] - 1 - butyric acid hydrochloride is prepared by acid hydrolysis of the corresponding 1-butyronitrile hydrochloride derivative. 1- Trifluoromethylanthracene is prepared by treatment of 1-anthracene-carboxylic acid with hydrogen fluoride and sulphur tetrafluoride; and 1,5-ditrifluoromethylanthracene is prepared analogously. 1-Propionyl-9<SP>1</SP>,10<SP>1</SP>-dihydro-spiro- [azetidine-3,11<SP>1</SP>-9,10-ethanoanthracene is prepared by reaction of the corresponding 1-unsubstituted derivative with propionyl chloride. 9<SP>1</SP>,10<SP>1</SP> - Dihydro - 9<SP>1</SP>,10<SP>1</SP> - dimethyl - 1 - trifluoroacetyl - spiro[azetidine - 3,11<SP>1</SP> - 9,10 - ethanoanthracene] is prepared by treatment of 9<SP>1</SP>,10<SP>1</SP>- dihydrospiro[azetidine-3,11<SP>1</SP>-9,10-ethanoanthracene] with trifluoroacetic anhydride, pyrolysis of the resulting 1-trifluoroacetyl-9<SP>1</SP>,10<SP>1</SP>-dihydrospiro[azetidine - 3,11<SP>1</SP> - 9,10 - ethanoanthracene], which is also novel, and reaction of the resulting 1-trifluoroacetyl-3-methylene-azetidine with 9,10- dimethylanthracene. Pharmaceutical compositions having antiinflammatory activity comprise, as active ingredient, a spiroazetidine-ethanoanthracene of the first general formula above or a non-toxic, pharmaceutically acceptable acid addition salt thereof, together with a pharmaceutical carrier or diluent, and may be administered orally or parenterally.